SIRT1 rs10823108 and FOXO1 rs17446614 responsible for genetic susceptibility to diabetic nephropathy

Abstract

SIRT1 and FOXO1 play an important role in the pathogenesis of diabetic nephropathy (DN). However, the association between genetic polymorphisms and susceptibility to type 2 DN (T2DN) has not been explored. In this study, a total of 1066 patients with type 2 diabetes mellitus (T2DM) (413 without and 653 with DN) were enrolled. The genotypes of three htSNPs (rs3818292, rs4746720, rs10823108) within SIRT1 and two htSNPs (rs2721068, rs17446614) in FOXO1 were determined by PCR-RFLP. HbA1C, LDL, HDL, TC, and TG levels were also examined. SIRT1 rs10823108 AA genotype was significantly associated with a decreased risk of DN (OR = 0.60, 95%CI: 0.38–0.97), while GA genotype (OR = 1.77, 95%CI: 1.33–2.35) and AA genotype (OR = 2.32, 95%CI: 1.25–4.34) of FOXO1 rs17446614 was associated with an increased T2DN risk. The interactions among rs1744 6614, BMI and duration of diabetes (OR: 2.63, 95%CI: 1.23–4.31) were also observed. Subsequent haplotype analysis revealed that two haplotype defined by AC (OR: 1.50, 95%CI: 1.15–1.94) and AT (OR: 1.79, 95%CI: 1.06–2.80) within FOXO1 gene may increase the risk of T2DN. In conclusion, genetic variant rs10823108 in SIRT1 and variant rs17446614 in FoxO1 may contribute to the risk of DN in T2DM patients.

<p>The Serum Concentration of Anti-Aging Proteins, Sirtuin1 and αKlotho in Patients with End-Stage Kidney Disease on Maintenance Hemodialysis</p>

“…Due to a wide expression and impact on the action of various proteins and gene transcription it may affect kidney function in many different ways. Genetic studies revealed relationship between SIRT1 gene polymorphisms and diabetic kidney disease 11,12 as well as association with carotid atherosclerosis in the SAPHIR cohort (The Salzburg Atherosclerosis Prevention Program in subjects at High Individual Risk), 25 which involved 1770 healthy unrelated white persons aged 39-67. Studies on Japanese hemodialysis patients also proved a significant association between SIRT1 polymorphisms, rs7069102 and rs2273773 and abnormal cholesterol metabolism and coronary artery calcification.…”

“…1,9,10 By far, SIRT1 is an important nephroprotective factor, especially in the diabetic kidney disease. 11,12 Its renal overexpression is an answer to oxidative stress. Klotho is mainly produced in the kidneys.…”

SIRT1 accelerates the progression of activity-based anorexia

“…For genotype association studies, seven SNPs were selected due to their prior association with metabolic disorders [69][70][71][72][73][74] . SIRT1 SNPs associated with metabolic disorders but not on the chips were excluded.…”

Urinary Exosomal MiRNA-4534 as a Novel Diagnostic Biomarker for Diabetic Kidney Disease

“…It is well-known that studies on the pathogenesis of DKD are increasingly focused on inflammatory responses ( 31 ), and FOXO is one of the most well-known pathways. Our research group has been working on the pathogenesis of DKD for a long time and has investigated the role of FOXO1 variant in DKD for the first time ( 32 ). There is considerable evidence that FOXO1 is a regulator of autophagy ( 33 ), and a novel mechanism of vascular complications in diabetes has been found ( 34 ), namely, FOXO1 inhibits the expression of Atg14 to destroy autophag-lysosomal fusion, thereby mediating age-induced autophagy apoptosis in endothelial cells (ECs).…”